Program Operations Manual System (POMS)

Canavan disease (CD) is a severe progressive inherited (genetic) disorder of the central nervous system
(CNS). It is one of the most common cerebral degenerative diseases of infancy, is
a gene-linked, neurological birth disorder in which the white matter of the brain
degenerates into spongy tissue riddled with microscopic fluid-filled spaces. CD is
one of a group of genetic disorders known as the leukodystrophies. These diseases
cause imperfect growth or development of the myelin sheath, the fatty covering that
acts as an insulator around nerve fibers in the brain. Myelin, which lends its color
to the “white matter” of the brain, is a complex substance made up of at least ten
different chemicals. Each of the leukodystrophies affects one (and only one) of these
substances. CD is caused by mutations in the gene for an enzyme called aspartoacylase.
Symptoms of CD, which appear in early infancy and progress rapidly, may include intellectual
disability, loss of previously acquired motor skills, feeding difficulties, abnormal
muscle tone (floppiness or stiffness), and an abnormally large, poorly controlled
head. Paralysis, blindness, or hearing loss may also occur. Children are characteristically
quiet and apathetic. Although CD may occur in any ethnic group, it is more frequent
among Ashkenazi Jews from eastern Poland, Lithuania, and western Russia, and among
Saudi Arabians.

The test to confirm diagnosis is a full gene sequence analysis of ASPA. Gross deletion/duplication
analysis of the entire ASPA gene is performed to detect known and potential novel
gross deletions.

TREATMENT

There is no cure, nor is there a standard course of treatment. Treatment is symptomatic
and supportive.

PROGRESSION

CD causes brain tissue atrophy cystic cavities resulting in enlargement of the brain
and head size. The prognosis for CD is poor. Death usually occurs before age 4.

SUGGESTED PROGRAMMATIC ASSESSMENT*

Suggested MER for Evaluation: The diagnosis is confirmed by genetic testing revealing a mutation in the gene for
the aspartoacylase enzyme.

Suggested Listings for Evaluation:

DETERMINATION

LISTING

REMARKS

Meets Listing

110.08

Canavan Disease confirmed by genetic testing or by laboratory testing for NAA.

111.17

Medical Equals

110.08

Listing 110.08 requires that the impairment be established by genetic testing. In
place of CD established by genetic testing, substitute CD established by typical history
and neurological findings along with neuroimaging studies with cerebral abnormalities
associated with CD.

* Adjudicators may, at their discretion, use the Medical Evidence of Record or Listings
suggested to evaluate the claim. However, the decision to allow or deny the claim
rests with the adjudicator.